Open AccessAnti-inflammatory Effects of Alcohol Are Associated with JNK-STAT3 Downregulation in an In Vitro Inflammation Model in HepG2 Cells
Author(s) -
Katharina Mörs,
Ramona Sturm,
Jason-Alexander Hörauf,
Shinwan Kany,
Paola Cavalli,
Jazan Omari,
Maciej Powerski,
Alexey Surov,
Ingo Marzi,
Aleksander J. Nowak,
Borna Relja
Publication year - 2021
Publication title -
disease markers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 66
eISSN - 1875-8630
pISSN - 0278-0240
DOI - 10.1155/2021/6622701
Subject(s) - inflammation , in vitro , chemistry , stimulation , downregulation and upregulation , lipopolysaccharide , tumor necrosis factor alpha , stat3 , viability assay , pharmacology , immunology , signal transduction , medicine , endocrinology , biochemistry , gene
Background In several preclinical and in vitro models of acute inflammation, alcohol (ethanol, EtOH) has been described as an immunomodulatory agent. Similarly, in different pathologies, clinical observations have confirmed either pro- or anti-inflammatory effects of EtOH. The liver plays an important role in immunity and alcohol metabolism; therefore, we analysed dose- and time-dependent effects of EtOH on the inflammatory response of human liver cells in an in vitro model of acute inflammation.Methods HepG2 cells were stimulated with IL-1 β and subsequently exposed to EtOH in a low or high dose (85 mM, LoD or 170 mM, HiD) for 1 h (acute exposure) or 72 h (prolonged exposure). IL-6 and TNF- α release was determined by ELISA. Cell viability, adhesion of isolated neutrophils to HepG2 monolayers, their ICAM-1 expression, and the activation of stress-induced protein kinase/c-Jun N-terminal kinase (SAPK/JNK) or signal transducer and activator of transcription 3 (STAT3) were analysed.Results In this experimental design, EtOH did not markedly change the cell viability. Acute and prolonged exposure to EtOH significantly reduced dose-independent IL-1 β -induced IL-6 and TNF- α release, as well as adhesion capacity to pretreated HepG2 cells. Acute exposure to EtOH significantly decreased the percentage of ICAM-1-expressing cells. IL-1 β stimulation notably increased the activation of SAPK/JNK. However, low-dose EtOH exposure reduced this activation considerably, in contradiction to high-dose EtOH exposure. Acute exposure to LoD EtOH significantly diminished the IL-1 β -induced STAT3 activation, whereas an acute exposure of cells to either HiD EtOH or in a prolonged setting showed no effects on STAT3 activation.Conclusion EtOH exerts anti-inflammatory potential in this in vitro model of hepatic inflammation. These effects are associated with the reduced activation of JNK/STAT3 by EtOH, particularly in the condition of acute exposure to low-dose EtOH.